Lansoprazole is chemically known as 2-(2-Benzimidazolylsulfinylmethyl)-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine. It is a H+/K+-ATPase Inhibitor and has the following structural formula:

Lansoprazole is specifically known from U.S. Pat. No. 4,628,098. Lansoprazole is an anti-ulcer drug and it is marketed as Prevacid ® by TAP Pharmacetuicals Products Inc.
The preparation of Lansoprazole by conventional methods is always accompanied by the formation of small quantities of the corresponding sulfone derivative as an impurity. For example, U.S. Pat. No. 6,180,652 (“the '652 patent”) describes the presence of sulfone derivative. Formation of sulfone derivative brings about the drawback of low yield of the desired sulfoxide. Although attempts have been made to separate the sulfone derivative from Lansoprazole, it is not a simple task, given their very similar structures and physicochemical properties. For this purpose the '652 patent describes a method that permits separation of Lansoprazole from its sulfone derivative and discloses an acetone complex of the Lansoprazole salt.
U.S. Pat. No. 5,578,732 patent describes the crystallization of Lansoprazole using an ethanol:water solvent system.
U.S. Pat. No. 6,002,011 (the '011 patent) describes the crystallization of Lansoprazole from the same ethanol:water system, containing traces of ammonia (0.03 mole NH4OH:1 mole Lansoprazole). The '011 patent discloses a reslurry method in water, which permits to obtain more stable “solvent free” Lansoprazole. The '011 patent fails to disclose the level of purity for Lansoprazole.
U.S. Pat. No. 6,909,004 patent claims a method of purifying Lansoprazole to obtain Lansoprazole having less than about 0.1%, wt/wt, water comprising the steps of: a) providing a solution of Lansoprazole in a solvent selected from an organic solvent (especially ethanol, which is disclosed) or a mixture of organic solvent and water in the presence of an amine compound (ammonia, ammonium hydroxide, diethyl amine, triethyl amine, or methyl amine), wherein the amine compound is present at a ratio of about 1:1, mole:mole, relative to Lansoprazole; b) combining the provided solution with an acid; c) isolating the Lansoprazole; d) dissolving the isolated Lansoprazole in an organic solvent selected from the group consisting of acetone, 2-butanone, methanol, dimethyl-carbonate, and diethyl-carbonate; and e) isolating the purified Lansoprazole having less than about 0.1%, wt/wt, water.
The U.S. Pat. No. 7,060,837 patent claims a method of purifying Lansoprazole, comprising the steps of: a) providing a solution of Lansoprazole in a solvent selected from an organic solvent (acetone, 2-butanone, dimethyl-formamide and tetrahydrofuran, ethanol, methanol, n-propanol, and i-propanol) or a mixture of organic solvent and water in the presence of an amine compound (ammonia, ammonium hydroxide, diethylamine, triethylamine and methylamine); b) combining the provided solution with an acid (acetic acid, formic acid, and hydrochloric acid), and c)isolating the purified Lansoprazole.
The U.S. Pat. No. 7,022,859 patent claims a method of preparing a Lansoprazole containing less than about 0.1% (wt/wt) water, comprising the steps of: a) crystallizing a Lansoprazole from solution in a solvent that is an organic solvent (acetone, 2-butanone, methanol, dimethyl-carbonate, and diethyl-carbonate) or a mixture of an organic solvent and water; and b) isolating the Lansoprazole containing less than about 0.1% (wt/wt) water.
Lansoprazole tends to lose stability and undergo decomposition when contaminated with traces of a solvent particularly water in their crystal structure. It is desirable that the Lansoprazole crystals be solvent free (i.e., residual solvent should be reduced to a minimum).
There is continuing need to obtain Lansoprazole which are free of contaminants including sulfone and sulfide derivatives.
We focused our research to develop an improved and efficient process for the purification of the compound of formula (I) in commercial scale using a solvent in presence of an alkali salt of an organic acid or in presence of an organic base such as piperidine or imidazole.
The disclosed process has advantages of simple operations, higher yield and purity, mild reaction conditions, and is suitable for industrial production over the processes described in the related prior arts.